The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study.

BACKGROUND: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. METHODS: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. RESULTS: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. CONCLUSIONS: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). REGISTRATION: https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Exercise-induced amplification of mitogen-stimulated oxidative burst in whole blood is strongly influenced by neutrophil counts during and following exercise.

This study characterized the effect of moderate- or vigorous-intensity exercise on leukocyte counts, using fingertip sampling, and mitogen-stimulated oxidative burst, measured in whole blood with a point-of-care test. In a randomized crossover design, 13 healthy adults (mean ± SD age: 22 ± 2 years; seven male, six female) cycled for 30-min, once at 52 ± 5% V˙ O2peak and on another occasion at 74 ± 9% V˙ O2peak . Blood was sampled at baseline, immediately post-exercise, and 15- and 60-min post-exercise. The leukocyte differential and mitogen-stimulated Reactive Oxygen Species (ROS) production were assessed. Lymphocytes increased immediately post-exercise and decreased below pre-exercise levels 15- and 60-min later. Lymphocyte mobilization immediately post-exercise was 59 ± 36% greater with vigorous- compared to moderate-intensity exercise (p < 0.01). Neutrophils increased immediately after exercise (38 ± 19%, p < 0.01) remaining elevated 60-min later (50 ± 34%, p < 0.01; averaged across intensities) and did not differ between intensities (p = 0.259). Mitogen-stimulated ROS production was amplified immediately (+32 ± 37%, p < 0.01) and 60-min post-exercise (+56 ± 57%, p < 0.01; averaged across intensities) compared to rest and did not differ with intensity (p = 0.739). Exercise-induced amplification of ROS production was abolished when correcting for neutrophil, monocyte and platelet counts and correlated most strongly with neutrophil mobilization immediately (r = 0.709, p < 0.01) and 60-min after vigorous exercise (r = 0.687, p < 0.01). Leukocyte kinetics can be assessed using fingertip blood sampling in exercise settings. Exercise-induced amplification of oxidative burst is detectable with a point-of-care test, but results are strongly influenced by neutrophil counts, which may not be routinely quantified.

Interventional laser surgery for oral potentially malignant disorders: a longitudinal patient cohort study.

Oral squamous cell carcinoma (OSCC) is a lethal disease, with rising incidence. There were 6767 new OSCC cases and 2056 deaths in the UK in 2011. Cancers are preceded by oral potentially malignant disorders (PMDs), recognizable mucosal diseases harbouring increased SCC risk, offering clinicians a 'therapeutic window' to intervene. Contemporary practice remains unable to predict lesion behaviour or quantify malignant transformation risk. No clear management guidelines exist and it is unclear from the literature whether early diagnosis and intervention prevents cancer. Between 1996 and 2014, 773 laser treatments were performed on 590 PMD patients in Newcastle maxillofacial surgery departments. The efficacy of the intervention was examined by review of the clinicopathological details and clinical outcomes of the patients (mean follow-up 7.3 years). Histopathology required up-grading in 36.1% on examining excision specimens. Seventy-five percent of patients were disease-free, mostly younger patients with low-grade dysplasia; 9% exhibited persistent disease and were generally older with proliferative verrucous leukoplakia. Disease-free status was less likely for erythroleukoplakia (P=0.022), 'high-grade' dysplasia (P<0.0001), and with lichenoid inflammation (P=0.028). Unexpected OSCC was identified in 12.0%, whilst 4.8% transformed to malignancy. Interventional laser surgery facilitates definitive diagnosis and treatment, allows early diagnosis of OSCC, identifies progressive disease, and defines outcome categories. Evidence is lacking that intervention halts carcinogenesis. Multicentre, prospective, randomized controlled trials are needed to confirm the efficacy of surgery.

Exercise-induced B cell mobilisation: Preliminary evidence for an influx of immature cells into the bloodstream.

The number of peripheral blood B lymphocytes doubles during acute exercise, but the phenotypic composition of this response remains unknown. In two independent exercise studies, using complimentary phenotyping strategies, we investigated the mobilisation patterns of distinct B cell subsets. In study one, nine healthy males (mean±SD age: 22.1±3.4years) completed a continuous cycling bout at 80% V̇O2MAX for 20min. In study two, seven healthy experienced cyclists (mean±SD age: 29.9±4.7years) completed a 30min cycling trial at a workload corresponding to +5% of the individual blood lactate threshold. In study one, CD3-CD19+ B cell subsets were classified into immature (CD27-CD10+), naïve (CD27-CD10-), memory (CD27+CD38-), plasma cells/plasmablasts (CD27+CD38+) and finally, recently purported 'B1' cells (CD27+ CD43+ CD69-). In study two, CD20+ B cells were classified into immature (CD27-IgD-), naïve (CD27-IgD+), and IgM+/IgG+/IgA+ memory cells (CD27+IgD-). Total B cells exhibited a mean increase of 88% (study one) and 60% (study two) during exercise. In both studies, immature cells displayed the greatest increase, followed by memory cells, then naïve cells (study one: immature 130%>mature 105%>naïve 84%; study two: immature 110%>mature 56%>naïve 38%). Our findings show that, unlike T cells and NK cells, B cell mobilisation is not driven by effector status, and, for the first time, that B cell mobilisation during exercise is comprised of immature CD27- IgD-/CD10+ cells.

A comparison of two commercially available ELISA methods for the quantification of human plasma heat shock protein 70 during rest and exercise stress.

This study compared resting and exercise heat/hypoxic stress-induced levels of plasma extracellular heat shock protein 70 (eHSP70) in humans using two commercially available enzyme-linked immunosorbent assay (ELIS)A kits. EDTA plasma samples were collected from 21 males during two separate investigations. Participants in part A completed a 60-min treadmill run in the heat (HOT70; 33.0 ± 0.1 °C, 28.7 ± 0.8 %, n = 6) at 70 % V̇O2max. Participants in part B completed 60 min of cycling exercise at 50 % V̇O2max in either hot (HOT50; 40.5 °C, 25.4 relative humidity (RH)%, n = 7) or hypoxic (HYP50; fraction of inspired oxygen (FIO2) = 0.14, 21 °C, 35 % RH, n = 8) conditions. Samples were collected prior to and immediately upon termination of exercise and analysed for eHSP70 using EKS-715 high-sensitivity HSP70 ELISA and new ENZ-KIT-101 Amp'd(™) HSP70 high-sensitivity ELISA. ENZ-KIT was superior in detecting resting eHSP70 (1.54 ± 3.27 ng · mL(-1); range 0.08 to 14.01 ng · mL(-1)), with concentrations obtained from 100 % of samples compared to 19 % with EKS-715 assay. The ENZ-KIT requires optimisation prior to running samples in order to ensure participants fall within the standard curve, a step not required with EKS-715. Using ENZ-KIT, a 1:4 dilution allowed for quantification of resting HSP70 in 26/32 samples, with a 1:8 (n = 3) and 1:16 (n = 3) dilution required to determine the remaining samples. After exercise, eHSP70 was detected in 6/21 and 21/21 samples using EKS-715 and ENZ-KIT, respectively. eHSP70 was increased from rest after HOT70 (p < 0.05), but not HOT50 (p > 0.05) or HYP50 (p > 0.05) when analysed using ENZ-KIT. It is recommended that future studies requiring the precise determination of resting plasma eHSP70 use the ENZ-KIT (i.e. HSP70 Amp'd(®) ELISA) instead of the EKS-715 assay, despite additional assay development time and cost required.

Monitoring changes in thioredoxin and over-oxidised peroxiredoxin in response to exercise in humans.

INTRODUCTION: Peroxiredoxin (PRDX) and thioredoxin (TRX) are antioxidant proteins that control cellular signalling and redox balance, although their response to exercise is unknown. This study aimed to assess key aspects of the PRDX-TRX redox cycle in response to three different modes of exercise. METHODS: Healthy males (n = 10, mean ± SD: 22 ± 3 yrs) undertook three exercise trials on separate days: two steady-state cycling trials at moderate (60% [Formula: see text]O2MAX; 27 min, MOD) and high (80% [Formula: see text]O2MAX; 20 min, HIGH) intensities, and a low-volume high-intensity interval training trial (10 × 1 min 90% [Formula: see text]O2MAX, LV-HIIT). Peripheral blood mononuclear cells were assessed for TRX-1 and over-oxidised PRDX (isoforms I-IV) protein expression before, during, and 30 min following exercise (post + 30). The activities of TRX reductase (TRX-R) and the nuclear factor kappa B (NF-κB) p65 subunit were also assessed. RESULTS: TRX-1 increased during exercise in all trials (MOD, + 84.5%; HIGH, + 64.1%; LV-HIIT, + 205.7%; p < 05), whereas over-oxidised PRDX increased during HIGH only (MOD, - 28.7%; HIGH, + 202.9%; LV-HIIT, - 22.7%; p < .05). TRX-R and NF-κB p65 activity increased during exercise in all trials, with the greatest response in TRX-R activity seen in HIGH (p < 0.05). DISCUSSION: All trials stimulated a transient increase in TRX-1 protein expression during exercise. Only HIGH induced a transient over-oxidation of PRDX, alongside the greatest change in TRX-R activity. Future studies are needed to clarify the significance of heightened peroxide exposure during continuous high-intensity exercise and the mechanisms of PRDX-regulatory control.

The antioxidant enzyme peroxiredoxin-2 is depleted in lymphocytes seven days after ultra-endurance exercise.

PURPOSE: Peroxiredoxin-2 (PRDX-2) is an antioxidant and chaperone-like protein critical for cell function. This study examined whether the levels of lymphocyte PRDX-2 are altered over 1 month following ultra-endurance exercise. METHODS: Nine middle-aged men undertook a single-stage, multi-day 233 km (145 mile) ultra-endurance running race. Blood was collected immediately before (Pre), upon completion/retirement (Post), and following the race at Day 1, Day 7 and Day 28. Lymphocyte lysates were examined for PRDX-2 by reducing and non-reducing SDS-PAGE with western blotting. In a sub-group of men who completed the race (n = 4), PRDX-2 oligomeric state (indicative of redox status) was investigated. RESULTS: Ultra-endurance exercise caused significant changes in lymphocyte PRDX-2 (F(4,32) 3.409, p = 0.020, η(2) = 0.299): 7 days after the race, PRDX-2 levels in lymphocytes had fallen to 30% of pre-race values (p = 0.013) and returned to near-normal levels at Day 28. Non-reducing gels demonstrated that dimeric PRDX-2 (intracellular reduced PRDX-2 monomers) was increased in three of four race completers immediately post-race, indicative of an 'antioxidant response'. Moreover, monomeric PRDX-2 was also increased immediately post-race in two of four race-completing subjects, indicative of oxidative damage, which was not detectable by Day 7. CONCLUSIONS: Lymphocyte PRDX-2 was decreased below normal levels 7 days after ultra-endurance exercise. Excessive accumulation of reactive oxygen species induced by ultra-endurance exercise may underlie depletion of lymphocyte PRDX-2 by triggering its turnover after oxidation. Low levels of lymphocyte PRDX-2 could influence cell function and might, in part, explain reports of dysregulated immunity following ultra-endurance exercise.

Comparisons of calculations with PARTRAC and NOREC: transport of electrons in liquid water.

Monte Carlo computer models that simulate the detailed, event-by-event transport of electrons in liquid water are valuable for the interpretation and understanding of findings in radiation chemistry and radiation biology. Because of the paucity of experimental data, such efforts must rely on theoretical principles and considerable judgment in their development. Experimental verification of numerical input is possible to only a limited extent. Indirect support for model validity can be gained from a comparison of details between two independently developed computer codes as well as the observable results calculated with them. In this study, we compare the transport properties of electrons in liquid water using two such models, PARTRAC and NOREC. Both use interaction cross sections based on plane-wave Born approximations and a numerical parameterization of the complex dielectric response function for the liquid. The models are described and compared, and their similarities and differences are highlighted. Recent developments in the field are discussed and taken into account. The calculated stopping powers, W values, and slab penetration characteristics are in good agreement with one another and with other independent sources.

Targeting of Th1-associated chemokine receptors CXCR3 and CCR5 as therapeutic strategy for inflammatory diseases.

CXCR3 and CCR5 are chemokine receptor that are predominantly expressed on the surface of Th1 polarized T cells. In a variety of human and experimental autoimmune diseases the enhanced expression of CXCR3 and CCR5 binding chemokine ligands is followed by the recruitment of CXCR3- and CCR5-positive T cells, indicating an important role for these chemokine receptors in T cell-mediated tissue damage. In this review, we summarize a number of in vivo studies available on the neutralization of CXCR3 and CCR5 in inflammatory disease, and specifically focus on the potential therapeutic effects of CXCR3 and CCR5 blockade in human autoimmune disease and organ transplantation.

Ruminal in situ disappearance kinetics of nitrogen and neutral detergent insoluble nitrogen from common crabgrass forages sampled on seven dates in northern Arkansas.

Southern crabgrass (Digitaria ciliaris [Retz.] Koel.) is often an undesirable species in field and forage crops, but visual observations suggest that livestock prefer it to many other summer forages. The objectives of this study were to assess the nutritive value of crabgrass sampled weekly between July 11 and August 22, 2001 and then to determine ruminal in situ disappearance kinetics of N and neutral detergent insoluble N (NDIN) for these forages. A secondary objective was to compare these kinetic estimates for crabgrass with those of alfalfa (Medicago sativa L.), bermudagrass (Cynodon dactylon [L.] Pers.), and or-chardgrass (Dactylis glomerata L.) as control hays. All kinetic evaluations were conducted with 5 ruminally cannulated Gelbvieh x Angus x Brangus steers (383 +/- 22.7 kg). Concentrations of N for crabgrass decreased linearly (P < or = 0.002) across sampling dates for leaf, stem, and whole-plant tissues. Conversely, percentages of the total N pool within NDIN and ADIN fractions generally increased over sampling dates in mostly linear patterns. For crabgrass, the immediately soluble portion of the total N pool (fraction A; overall mean = 54.6% of N) was greater (P < 0.001) than for all control hays. Crabgrass exhibited a more rapid N disappearance rate (overall mean = 0.093/h; expressed as a proportion disappearing/h) than that of bermudagrass (0.046/h; P < 0.001), but the disappearance rate for alfalfa N (0.223/h) was considerably faster (P < 0.001) than for crabgrass. The effective ruminal disappearance of N was greater (P < 0.001) for crabgrass (overall mean = 85.4%) than for the alfalfa (83.3%), bermudagrass (72.3%), or orchardgrass (76.0%) control hays. For alfalfa, the ruminal disappearance rate of NDIN (0.150/h) was more rapid (P < 0.001) than for crabgrass (overall mean = 0.110/h); however, the disappearance rate for crabgrass was faster than that for bermudagrass (0.072/h; P < 0.001) or for orchardgrass (0.098/h; P = 0.010). Effective ruminal disappearance of NDIN was greater (P < 0.001) for crabgrass (overall mean = 72.0%) than for the bermudagrass (69.0%) or alfalfa hays (50.5%), but there was no difference (P = 0.865) between crabgrass and orchardgrass (72.1%). Although crabgrass forages exhibited concentrations of total N that were comparable with those of alfalfa and rates of ruminal N disappearance that were < 50% of those for the alfalfa hay control, improvements in N use efficiency relative to alfalfa are questionable because of the excessively large Fraction A for crabgrass.

Effect of rotation frequency and weaning date on forage measurements and growth performance by cows and calves grazing endophyte-infected tall fescue pastures overseeded with crabgrass and legumes.

A grazing study was initiated in April 2000 and continued through three calving and weaning cycles (ending July 2003) to investigate the effects of rotational grazing management (twice monthly [2M] vs. twice weekly [2W]) and weaning date (mid-April [EARLY] vs. early June [LATE]) on production of fall-calving cow-calf pairs (495 +/- 9.6 kg initial BW) grazing Neotyphodium coenophialum-infected tall fescue (Festuca arundinacea Schreb.) overseeded with legumes and crabgrass. Secondary objectives of the experiment were to monitor differences in quantity and quality of available forage and to evaluate changes in forage species composition. Pastures were dominated by tall fescue throughout the study, and the proportion of basal cover was greater (P < 0.05) in 2M than in 2W pastures. The percentage of legumes was very low across all treatment combinations, but the percentage of crabgrass continued to increase (P < 0.05) linearly and quadratically across years for both summer and fall sampling periods, regardless of rotation or weaning program. In vitro DM disappearance and mineral concentrations varied minimally because of rotation frequency or weaning date. Rotation frequency did not substantially affect (P = 0.11 to 0.97) cow BW, hay offered, milk production, calving interval, calf birth weight, or actual or adjusted weaning weights; however, 2M cows had 0.3 units higher (P < 0.05) BCS at the time of breeding than 2W cows. Calves weaned late had greater (P < 0.05) actual weaning weight and weighed more (P < 0.05) on the LATE weaning date than on the EARLY weaning date, but 205-d adjusted weaning weights did not differ (P = 0.74) across weaning dates. Therefore, rotation frequency and/or weaning date had little effect on forage species composition or forage quality. In addition, the rapid rotation program offered little advantage with respect to animal performance, and weaning fall-born calves grazing endophyte-infected tall fescue pastures at approximately 189 d of age seemed to be detrimental to calf performance compared with delaying weaning until 243 d of age.

Aerobic stability of wheat and orchardgrass round-bale silages during winter.

Using recently developed technology, balage is often stored in large (1.2 x 1.2 m) round bales that are wrapped in plastic film with an in-line wrapper. The aerobic stability of this fermented forage is important, particularly during winter months when it is fed to livestock or sold as a cash crop. Two types of forage, orchardgrass [Dactylis glomerata L.; 54.4% dry matter (DM)] and wheat (Triticum aestivum L.; 62.4% DM), were packaged in large round bales and wrapped with an in-line wrapper during May 2002. Twenty-one bales of each balage type were unwrapped and exposed to air on Dec. 10, 2002 for 0, 2, 4, 8, 16, 24, or 32 d (ambient temperature range = 0.6 to 19.4 degrees C) to evaluate aerobic stability. For both orchardgrass and wheat balage, final bale weight, concentration of DM, and pH were not affected by exposure time. Across both balage types, DM recoveries were > or = 97% for all bales, indicating that both balage types were very stable when exposed to air. For orchardgrass balage, exposure time had no effect on concentrations of NDF, ADF, hemicellulose, cellulose, or lignin, thereby indicating that little deterioration occurred. Similarly, no contrast relating any fiber component with exposure time was significant for wheat balage. Concentrations of crude protein (CP) were not affected by exposure time for wheat balage, but there was a tendency for exposed orchardgrass bales to have greater concentrations of CP than bales sampled on d 0. Exposure time had no effect on 48-h in situ digestibility of DM for wheat balage, but there was a tendency for a linear increase with exposure time for orchardgrass balage. However, the overall range (78.2 to 80.5%) over the 32-d exposure period was very narrow, and this response is probably of limited biological significance. Generally, concentrations of fermentation acids were low, primarily because of the high concentration of DM within these balages, and only minimal changes in these acids were observed over the exposure interval. These results suggest that the balage evaluated in this trial during winter conditions was very stable after exposure to air for up to 32 d. This should allow for considerable flexibility with respect to feeding, transport, and marketing of balage during winter months without significant aerobic deterioration.

Ruminal in situ disappearance kinetics of dry matter and fiber in growing steers for common crabgrass forages sampled on seven dates in northern Arkansas.

Southern crabgrass (Digitaria ciliaris [Retz.] Koel.) is often viewed as an undesirable weed, largely because it encroaches upon field and forage crops, gardens, and lawns. However, visual observations of livestock grazing mixed-species pastures suggest that cattle seem to prefer crabgrass to many other summer forages. The objectives of this study were to assess the nutritive value of crabgrass sampled weekly between July 11, and August 22, 2001, and then to determine ruminal in situ disappearance kinetics of DM and NDF for these crabgrass forages. A secondary objective was to compare these kinetic estimates with those of alfalfa (Medicago sativa L.), bermudagrass (Cynodon dactylon [L.] Pers.), and orchardgrass (Dactylis glomerata L.) control hays. All forages were evaluated in situ using five (383 +/- 22.7 kg) ruminally cannulated crossbred (Gelbvieh x Angus x Brangus) steers. Whole-plant crabgrass exhibited more rapid (P < or = 0.002) ruminal disappearance rates of DM (overall range = 0.069 to 0.084 h(-1)) than did bermudagrass (0.054 h(-1)) and orchardgrass (0.060 h(-1)) hays, but disappearance rates were slower (P < 0.001) for crabgrass than for alfalfa hay (0.143 h(-1)). Effective ruminal disappearance of DM was greater (P < 0.001) for crabgrass (overall range = 69.3 to 75.4%) than for all the control hays. Similarly, disappearance rates of NDF for crabgrass (overall range = 0.069 to 0.086 h(-1)) were more rapid (P < 0.001) than observed for bermudagrass and orchardgrass hays; however, NDF in alfalfa disappeared at a faster (P < 0.001) rate (0.107 h(-1)) than crabgrass. These results indicate that crabgrass offers greater effective ruminal degradability of DM and NDF than orchardgrass or alfalfa of moderate quality. More importantly, it potentially offers faster and more extensive ruminal disappearance than perennial warm-season grasses typically found throughout the southeastern United States, and it should likely support improved performance by ruminant livestock in this region.

Acetate non-utilizing mutants of Arabidopsis: evidence that organic acids influence carbohydrate perception in germinating seedlings.

A phenotypic screen was employed to isolate Arabidopsis plants that are deficient in their ability to utilize or sense acetate. The screening strategy, based on resistance to the toxic acetate analogue monofluoroacetic acid, was adapted from one that has been used successfully to identify important metabolic and regulatory genes involved in acetate metabolism in fungi. Following conventions established from the fungal work, the mutants were called acn mutants for acetate non-utilization. Three highly resistant plant lines were the focus of genetic and physiological studies. Mutant acn1 appears to be a true acetate non-utilizing mutant, as it displays increased sensitivity to exogenous acetate. The progeny of the original acn2 mutant did not germinate, even in the presence of sucrose as an exogenous carbon source. The germination of seeds from the F3 generation depended on the sucrose concentration in the medium. Only a small proportion of seeds germinated in the absence of exogenous sucrose and in the presence of 100 mM sucrose, but up to 70% of seeds germinated on 20 mM sucrose. Mutant acn3 exhibited sensitivity to exogenous sucrose, showing significant chlorosis on medium containing 20 mM sucrose, but no chlorosis when grown in the absence of exogenous sucrose. This phenotype was alleviated if acetate was provided. The acn mutants demonstrate that disrupting organic acid utilization can have profound affects on carbohydrate metabolism.

NOREC, a Monte Carlo code for simulating electron tracks in liquid water.

The work reported here was originally motivated by a discussion of Monte Carlo computer codes for electron transport in water given in Report No. 130 by the National Council on Radiation Protection and Measurements (NCRP). It was pointed out (correctly) that a published depth-dose distribution calculated by the Oak Ridge electron transport code, OREC, for 800 keV electrons normally incident on a water slab was apparently in error, possibly due to inadequate treatment of elastic scattering. In this paper we describe the replacement of the original OREC elastic cross sections by current ones from the National Institute of Standards and Technology (NIST). This investigation led also to the critical examination and revision of some other parts of the program, as described here. The revised code, which we have renamed NOREC, represents the first substantial review and modification of the Oak Ridge code in a number of years. We also present some comparisons of results calculated with the old and new versions and discuss their implications with respect to earlier studies. We have also written a version of NOREC in C++ language, which is available to other investigators. This paper provides a record of a response to the NCRP published statement and documentation for the revised code, NOREC.

Development of the response AC/A ratio over the first year of life.

This study investigated the development of the link from accommodation to vergence in infants by occluding one eye thus removing binocular cues. Occluded adults continue to converge partially demonstrating that the accommodative drive to vergence (the AC/A link) and proximal cues are sufficient to drive vergence. For infants of all ages, AC/A ratios were found to be in the normal adult range. We conclude that infants can use monocular cues to drive vergence and that this occurs before the age when there is a substantial increase in the accuracy of oculomotor processes. There is flexibility in the developing visual system which is able to produce early vergence responses by relying upon alternative cues.

Comparisons of in situ dry matter disappearance kinetics of wheat forages harvested by various techniques and evaluated in confined and grazing steers.

Ruminal in situ disappearance kinetics of forages are commonly evaluated in confined animals, but there have been relatively few attempts to evaluate disappearance kinetics of forage dry matter (DM) in grazing animals. Our objectives were 1) to evaluate the effects of harvest technique and sampling date on the in situ DM disappearance kinetics and nutritive value of wheat (Triticum aestiuum L.) forage, and 2) to compare the in situ disappearance kinetics of DM for these forages when the experimental steers were housed in confinement with those obtained from steers grazing wheat pasture. Wheat forage was harvested on three dates (March 6, March 27, and April 11, 2000). Sampling techniques evaluated on each date included three clipping techniques (whole plant, random pluck, and top half) and two evaluations of masticates (oven dried at 50 degrees C or lyophilized). There was an interaction of harvest technique and sampling date main effects for crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), hemicellulose, cellulose, lignin, and whole-plant ash. Disappearance kinetics of DM for these 15 forages were then evaluated by the in situ technique using five 393 +/- 54-kg crossbred steers consuming an alfalfa-based (Medicago sativa L.) diet in confinement, and subsequently, in five 448 +/- 49-kg crossbred steers grazing wheat pasture during March 2001. For fractions A, B, and C, potential extent, rate of disappearance (Kd), and effective ruminal degradability, linear regressions of values obtained for steers grazing wheat pasture on those obtained from confined cattle had significant slopes and exhibited high r2 statistics (>0.821). For fractions A and B, and Kd, the slope of these regression lines did not differ from unity, and the intercept did not differ from zero. For fraction C, potential extent of disappearance, and effective ruminal degradability, slopes were all equal to 1.19 and differed from unity. For effective degradability, deviation of the slope from unity can be explained, in part, on the basis of the passage rates used to calculate these values (0.035 and 0.062/h for confined and grazing steers, respectively). From a practical standpoint, the in situ disappearance kinetics of DM for these wheat forages did not appear to be altered substantially by evaluating them in grazing steers.

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares.

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.

Impact of heating-degree-day accumulation during bermudagrass hay storage on nutrient utilization by lambs.

Spontaneous heating in stored alfalfa (Medicago sativa) has reduced forage quality and DM and N digestibility through microbial respiration and Maillard polymer formation. The impact of heating-degree-day (HDD) accumulation in stored bermudagrass (Cynodon dactylon [L.] Pers.) was evaluated for its effect on nutrient utilization by lambs. Twenty Rambouillet wether lambs (53.1 +/- 0.74 kg) were used in a completely randomized total collection experiment. The hays selected for this study had previously undergone spontaneous heating, producing either 5, 119, 201, 273, or 401 HDD (> 35 degrees C) during a 60-d storage period. Lambs were offered diets of these hays at 1.5% of BW. Dry matter intake did not differ (P = 0.59) among hays. Linear relationships were detected between HDD and apparent digestibilities of DM (y = 59.1 - 0.016x; P < 0.01; R2 = 0.37), OM (y = 59.3 - 0.017x; P < 0.01; R2 = 0.43), NDF (y = 66.4 - 0.012x; P = 0.01; R2 = 0.30), and hemicellulose (y = 74.0 - 0.012x; P = 0.02; R2 = 0.27). Similarly, significant regressions were observed for fecal N excretion (g/d; y = 4.70 + 0.004x; P < 0.01; R2 = 0.68), apparent N absorbed (g/d; y = 7.4 - 0.005x; P < 0.01; R2 = 0.50), apparent N absorption (%; y = 61.2 - 0.038x; P < 0.01; R2 = 0.71), apparent neutral detergent insoluble nitrogen digestibility (%; y = 85.8 - 0.026x; P = 0.01; R2 = 0.73), and apparent acid detergent insoluble nitrogen digestibility (%; y = 1.5 + 0.101x; P < 0.01; R2 = 0.62). Therefore, spontaneous heating during the storage of bermudagrass hay has a negative effect on dry matter and fiber digestion and nitrogen absorption by lambs.